Table 1.

Summary of pharmacological studies on largazole (1).

Disease/Target	Significant Biological Activity	Reference
Angiogenesis-associated diseases	Topical application of the compound attenuated alkali-induced corneal neovascularization in mouse model. Down-regulated the expression of the pro-angiogenic factors and up-regulated the expression of the anti-angiogenic factors in vivo.	[31]
Lung cancer	Potently inhibits the proliferation and clonogenic activity in lung cancer cells. Arrests cell cycle at G1 phase and up-regulates the expression of cyclin-dependent kinase inhibitor p21 in lung cancer cells. An E2F1-targeting cell cycle inhibitor, which is overexpressed in lung cancer tumor.	[32]
Rheumatoid arthritis	Activates p38 and Akt pathways and increase expression of HDAC6 by more than 200% in rheumatoid arthritis synovial fibroblasts. Increases HDAC6 expression, which led to enhancement of the detrimental effects of TNF-α in RA synovial fibroblasts.	[33]
Liver fibrosis	Reduces liver fibrosis and angiogenesis by inhibition of transforming growth factor-b as well as vascular endothelial growth factor signalling.	[34]
Breast cancer	Cooperates with dexamethasone to induce localization of E-cadherin to the plasma membrane in breast cancers as well as to suppress in vitro cellular invasion of cancer cells.	[35]
Protein ubiquitination	Largazole and its ester and ketone analogs selectively inhibit ubiquitin conjugation to p27Kip1 and TRF1 in vitro.	[36]
Epstein-Barr virus (EBV)-associated lymphomas	Induces expression of EBV lytic-phase gene and sensitize lymphoma cells to nucleoside antiviral drugs.	[37]
Bone-related disorders	Exhibits in vitro and in vivo osteogenic activity via increased expression of Runx2 (runt-related transcription factor 2) and BMPs (bone morphogenetic proteins). Induces expression of alkaline phosphatase (ALP) and osteopontin (OPN).	[38]
Colon cancer	Strongly stimulated histone hyperacetylation in tumor in vivo by using a human HCT116 xenograft mouse model. Efficacy in inhibiting tumor growth and induced apoptosis in the tumor. Regulates transcription of genes involved in the induction of cell cycle arrest and apoptosis.	[39]
Oncogenic super-enhancers	Decreases RNA polymerase II accumulation at super-enhancers (SEs) and preferentially suppresses SE-driven transcripts associated with oncogenic activities in transformed cells.	[40]
Antiretroviral therapy	Combination of largazole and bryostatin analogues are potent activators of latent HIV without global T-cell activation within resting CD4+ T-cells.	[41]